Pharmacovigilance in the EU: a closer look at EudraVigilance

Health Europa highlights the role of EudraVigilance in the pharmacovigilance activities of the EMA, from the launch of the revamped system in 2017 to Brexit and beyond.

The European Medicines Agency (EMA) is the main EU body responsible for pharmacovigilance, which it defines as the ‘science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem’. Whereas EudraVigilance is essentially the system for monitoring the safety of medicines.

Such monitoring extends well beyond the clinical trial phase, which takes place before a medicine is authorised for use and involves only a limited number of people and continues for as long as a medicine is in use in healthcare practice.

Within the EMA, PRAC – the Pharmacovigilance Risk Assessment Committee – is tasked with assessing and monitoring the safety of human medicines. A relatively new body (it was formally established just six years ago in 2012), PRAC is responsible for detecting, assessing, minimising and communicating the risk of adverse reactions; designing and evaluating post-authorisation safety studies; and the pharmacovigilance audit.

An overview of EudraVigilance

Central to the pharmacovigilance activities of the EMA and PRAC is EudraVigilance, which the EMA describes as a ‘comprehensive system for managing and analysing information on suspected adverse reactions to medicines authorised in the European Economic Area (EEA)’. EudraVigilance acts as a type of ‘one-stop shop’ for reporting suspected adverse reactions in both healthcare practice and clinical trials.

The EMA and national competent authorities in EU and EEA Member States are responsible for reviewing and analysing the information stored within the EudraVigilance database in order to detect safety signals. These are then evaluated by PRAC, who decides whether or not regulatory action should be recommended. EudraVigilance data is also available – to varying degrees – to other stakeholders, including patients, in an effort to improve not only safety monitoring but also research.

According to the EMA, as of the end of 2017, EudraVigilance contained information on upwards of 12.45 million safety reports, implicating 7.95 million cases, and 744,219 medicinal products on the market in the EU.¹

Benefits of the revised EudraVigilance

In November 2017, a new, enhanced version of EudraVigilance was launched.2 The revised system is intended to ensure that marketing authorisation holders (MAHs) and clinical trial sponsors can more easily report any suspected adverse reactions, the ultimate aim being increased patient safety.

The EMA lists several advantages of the new system, among them:

Simplified reporting of individual case safety reports ((ICSRs) which the EMA defines as documents ‘providing information related to an individual case of a suspected side effect due to a medicine’) and less duplication of efforts

• Improved detection of new or changing safety issues
• Better interoperability thanks to the use of an agreed standard for ICSRs
• Improved searchability and data analysis
• Enhanced system capacity to support large volumes of users and reports
• Stronger collaboration with the World Health Organization.

EudraVigilance Operational Plan

Earlier this year, PRAC adopted the EudraVigilance Operational Plan: Milestones 2018 to 2020, which sets out the main activities and developments scheduled in the next two and a half years and how they are expected to impact on both EudraVigilance and its stakeholders, including MAHs, national competent authorities, and the EMA.¹

These developments include the launch of the new General Data Protection Regulation (GDPR), which, although not directly applicable to the EMA, will affect EudraVigilance users, as well as the UK’s withdrawal from the EU, which is currently expected to take place on 29 March 2019 and will have a direct impact on the UK’s relationship with the EMA. It remains to be seen exactly how Brexit will impact pharmacovigilance and thus patient safety in the European Union and United Kingdom.

The European Network of Centres for Pharmacoepidemiology and Pharmacovigilance

Co-ordinated by the EMA, the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP®) has the main goal of strengthening the monitoring of the risk-benefit balance of medicinal products in Europe. To this end, the network, which brings together public institutions and contract research organisations, works to foster co-operation between all involved actors, develop and maintain methodological standards and governance principles for related research, and facilitate high-quality, collaborative, independent post-authorisation studies.

In March, Xavier Kurz, Susana Perez-Gutthann and members of the ENCePP Steering Group told Health Europa Quarterly’s sister publication, SciTech Europa Quarterly, more about ENCePP’s achievements since its launch in June 2007. The following is an extract of that article.

‘The ENCePP has been created in a heterogeneous landscape of academic centres, research organisations and database owners, and a changing regulatory environment in pharmacovigilance and pharmacoepidemiology. There was therefore a risk that differing priorities and constraints would lead to divergent routes after an initial period of collaboration.

‘We believe that several factors explain that ENCePP achieved important outcomes from its onset and remained a coherent, dynamic, and active network over 10 years:

• A recognised need for collaboration to address limitations in the pharmacoepidemiological landscape and keep abreast of methodological, regulatory, and organisational developments (e.g. increased use of existing data sources, new legislation on PASS, new funding opportunities)
• A firm commitment to common guiding principles of transparency, scientific independence, and quality standards
• An acknowledgment of the diversity in the centres’ domain of expertise and capacity
  to collaborate
• A strong governance based on an elected Steering group and several working groups, with the support from EMA
• The ability to meet face to face in plenary meetings on a periodic basis and to actively contribute to the development of good practice and regulatory guidance.

‘All these factors have been instrumental to foster and accelerate partnership between research centres and improve the implementation of collaborative studies.’

The full version of this article appeared as: Kurz X, Perez‐Gutthann S, the ENCePP Steering Group. Strengthening standards, transparency, and collaboration to support medicine evaluation: Ten years of the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP). Pharmacoepidemiol Drug Saf. 2018;1-11.

References

1. www.ema.europa.eu/documents/other/eudravigilance-operational-plan-milestones-2018-2020_en.pdf
2. www.ema.europa.eu/news/new-eudravigilance-system-live

This article will appear in issue 7 of Health Europa Quarterly, which will be published in November 2018.